Structural relations of illness perception, fatigue, locus of control, self-efficacy, and coping strategies in patients with multiple sclerosis: a cross-sectional study

Background Patients with multiple sclerosis (MS) experience extensive problems due to fatigue and illness perception. Reducing these problems may improve these patients’ quality of life (QoL). Accordingly, the current study is aimed at investigating the mediating role of self-efficacy, locus of control, coping strategy, and outcome expectancy in the relationship between illness perception and fatigue severity in patients with MS. Methods In a cross-sectional analytical study, data of 172 MS patients were collected by self-report questionnaires including illness perception questionnaires (IPQ-R), Multiple Sclerosis Self-Efficacy (MSSES) scale, health locus of control (MHLC), coping strategies in MS(CMSS), outcome expectancy, level of physical activity (IPAQ-SF), patient activation measure (PAM-13) and fatigue severity scale (FSS). The data were analyzed using linear and multiple regression analysis in SPSS software version 24 (SPSS Inc., Chicago, IL, USA). Results The final model explained 62% of the fatigue variance. Illness perception both directly and indirectly (through self-efficacy, physical activity level, internal health locus of control, patient activation, and negative coping strategies) could predict the participants’ fatigue severity. Among the mediating variables, internal health locus of control, self-efficacy, and negative coping strategies had the greatest impact, respectively. moreover, outcome expectancy variable did not a mediating role in the aforementioned relationship. Conclusions To enhance the well-being of MS patients and to improve the efficiency of treating MS related fatigue, a comprehensive treatment protocol is needed, encompassing psychological factors affecting fatigue severity.


Introduction
Multiple Sclerosis (MS) is a chronic illness of central nervous system (CNS) mostly involved young adults and there is poor understanding about that.It is the most prevailing cause of disability among the young productive population following the disability caused by incidences and it affects socio-economic status [1,2].This illness causes the life quality reduction, social isolation and unemployment [3].
Fatigue is defined as a feeling of lack of physical or mental energy or both by the individual or their caregiver so that interfere with the individual's favorite activities [2,4].It is a prevailing and debilitating symptom in patients with multiple sclerosis experienced as the most common symptom by over 80% of the affected ones [2,5,6] and reported by almost half of them as the most debilitating symptom even compared to physical pain and disability [7].So fatigue, as the most primary problematic factors in MS management, needs resourcefulness and providing protocols which can reduce fatigue [2,8,9].
This important subject confronts challenges given the various definitions and dimensions of fatigue such as mental and motor dimensions [10] or perceived fatigue and performance fatigability [6,11] which make an unified and comprehensive definition of fatigue impossible, as well as possible different ground mechanisms causing fatigue and the absence of a tool with sufficient comprehensiveness to evaluate and measure fatigue accurately [8].
In this research, an attempt was made to offer a final model applicable in psychological interferences of fatigue management by using the underlying psychological concepts.These concepts as study' variables are taken from Bandura's social learning [12], Julian Rutter's locus of control [13] and Lazarus and Folkman's stress and coping [14,15] theories, which several studies have examined the effect of each one on fatigue [16][17][18][19][20][21][22].Since we did not find that all these variables were examined in one study and with respect to the potentials of the integrated approach to psychotherapy [23], In the present study the following conceptual model (Fig. 1) was designed and studied the relationships between the variables and the effect of the model on the severity of fatigue.

Research design
This is a correlational type of cross-sectional analytical study that was conducted since June 2021 to December 2022 in MS Society (Qom, Iran).

Participants and method
The statistical population in the current studies was all MS diagnosed patients who were registered in Qom MS society and a random sample were selected from all eligible patients according to the inclusion and exclusion criteria.Inclusion criteria were patients with a definitive diagnosis of MS by a neurologist based on medical history and neurological examinations and having sufficient evidence to meet McDonald's criteria, aged between 18 and 60 and possessing at least educational level of third grade of middle school.Exclusion criteria include any physical or mental disability (Scores of 6 and above in EDSS were considered as physical disability and exclusion criteria.Also, a score of less than 22 in MMSE was determined as mental disability and one of the exclusion criteria).andcomorbidity and unwillingness to participate in the study.
Sample size calculation for this study was calculated based on considering study power 80%, confidence interval 90% and the correlation coefficient between health locus of control and fatigue (r = 0.153) according to the results of Choi study [24].Finally, the required sample size for this study estimated as 189 subjects according to our predictive variables in the current study and bellow formula [25].Due to possible specimens' attrition or any defects in completing the questionnaires, 200 individuals with MS from Qom MS Society were selected by simple random sampling and out of whom, 183 subjects received the questionnaires after signing the consent form to participate in the research.They were asked to gradually complete the questionnaires and return them to the society office at most in 2 weeks.Finally, by removing Fig. 1 Relations among variables in conceptual model deficit questionnaires data from 172 patients were used for analysis.

Measures
Different scales used in this study for data collection.Self-report illness perception questionnaires, self-efficacy scale in MS, health locus of control, coping strategy in MS, outcome expectancy, physical activity level, patient activation measure and fatigue severity scale were completed by subjects.Details of each instrument is described below.

Illness perception questionnaire (IPQ-R)
The questionnaire contains 43 items assessing the emotional expressions, treatment control, illness outcomes, acute/chronic timeline, illness coherence, personal control and periodic timeline [26].Validity coefficient of the Persian version was also obtained by Masoudnia in 1384 to range from 0.38 to 0.93 for seven components and also, it exhibited a good criteria and construct validity [27].In this study, Cronbach's alpha for components was obtained as 0.78 to 0.89.

Fatigue severity scale (FSS)
Fatigue severity scale was provided by Krupp and its scoring is done by patient and in a 7-point Likert scale.Score 1 indicates completely disagreed and score 7 means completely agreed and the resulted score will be in the range of 9 (nonexistence of fatigue) to 63 (maximum fatigue) [28].In examining the validity and reliability of the Persian version of fatigue severity scale, internal consistency is determined with Cronbach's alpha as 0.96, ICC coefficient equal to 0.93, and correlation coefficient equal to 0.73 [29].In this research, Cronbach 's alpha was obtained as 84%.

Multiple sclerosis self-efficacy scale (MSSES)
This tool is developed by Rigby et al. which is dimensional and self-report developed for adults and through 14 items it measures four dimensions namely independence and activity, worries and interests, personal control and social efficiency [30].In the study conducted in Iran, Cronbach' alpha of this scale and split-half coefficient were obtained as 0.90 and 0.87, respectively [31].The scoring of this scale is in a form of a 6-point Likert scale.In this research, Cronbach's alpha was obtained equal to 0.78.

Health Locus of Control (HLC)
This 18-item questionnaire, contains three 6 item subscales: internality; powerful others externality; and chance externality [32].Previous studies indicate the appropriateness of using the Persian version of this tool in Iranian populations [33].In current study, the subscale internal locus of control is used with 0.75 Cronbach's alpha.

Coping with multiple sclerosis scale (CMSS)
This tool is a 29-item self-report scale observing the main problem related to MS and questioning the strategy to deal with the problem [34].In Iran, Yavari's study suggested Cronbach alpha of negative and positive coping as 0.80 and 0.58, respectively and 0.80 in total; and coefficients resulted from Guttman's Split-Half Coefficient were reported as 0.71 and 0.55, respectively with a total of 0.73 [35].In this research, negative coping subscale with Cronbach's alpha of 0.85 was used aligned with negative illness perception.

Outcome expectancy scale
Several questionnaires have been developed so far for outcome expectancy in various areas which are mostly based on Bandura's social cognitive theory encompassing three areas namely physical, social and self-evaluative outcome expectancy [36].Cronbach's alpha coefficients for physical outcome expectancy, social outcome and self-evaluative outcome were 0.75, 0.82 and 0.84, respectively [37].In Iran, a scale possessing 13 items and Cronbach's alpha coefficient 0.87 has been designed and employed.Cronbach's alpha for the scale used in this research was 0.89.

International physical activity questionnaire-short form(IPAQ-SF)
Tool-measuring of the Iranian version of this questionnaire was examined by Baghiani-Moghaddam et al. [38].The results showed a content validity index of 0.85 and a content validity ratio of 0.77 while suggesting a good content validity.Moreover, its internal consistency was satisfying given a Cronbach's alpha coefficient of 0.70 and Spearman Brown's correlation coefficient of 0.90 indicated the goodness of test-retest reliability [39].

Patient activation measure (PAM-13)
Developed by Hibbard et al., this tool has 13 items.Each item can get a score ranged from one to four, corresponding respectively to strongly disagree, disagree, agree, and strongly agree.In a study in Iran on type-2 diabetic patients, the psychometric properties of this tool were confirmed [40].Cronbach's alpha of the used scale in this research was 0.87.

Mini-Mental State Examination (MMSE)
This tool is employed for briefly examining the cognitive status of individuals with 30-point test that examines 7 domains of cognition: orientation, registration, attention and calculation, recall, language, naming and visuospatial.The score obtained range from 0 to 30.0-9 scores indicates severe cognitive disorder, 10-19 indicates moderate cognitive disorder, 20-25 indicates mild cognitive disorder and 26 to 30 suggest the normal cognition [41].The validity of the Persian version was determined with Cronbach's alpha 0.78, sensitivity of 0.90, and specificity of 0.84 [42].

Ethical consideration
This study was approved by ethics committee, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran by ethical approval ID IR.USWR.REC.1398.020.After taking the ethical code, the patients invited to participate in the research and all participants were informed that their participation is voluntary.Moreover, written informed consent was obtained from all eligible subjects involved in the study.

Statistical analysis
Statistical analysis included descriptive and analytic analysis were done using SPSS software version 24 (SPSS Inc., Chicago, IL, USA).Mean and standard deviation used in descriptive analysis for the main variables under the study and followed by linear regression analysis (Enter method) to evaluate the fatigue severity variance.Pearson coefficients was used to assess the correlation of research variables.In addition, multiple regression analysis was used to determine the effect of each independent variable on fatigue severity.One of the basic presuppositions of multiple regression analysis is the independency of independent variables, in other words, lack of relation between the scores of independent variables error with each other (errors independency) which can be examined with the Durbin-Watson test.Durbin Watson test's result in this study is 1.92 which is within the permissible range of 1.5 to 2.5 or even close to the most acceptable value namely 2 [43].Besides the bivariate correlation matrix, tolerance statistics and Variance Inflation Factor (VIF) are also used in examining the lack of collinearity.Tolerance = 1-R 2 and Variance Inflation Factor (VIF) . Tolerance statistics ranges is from 0 to 1, if its value is equal to or less than 0.01 for a variable it indicates multicollinearity.Another method is calculating the variance inflation factor (inverse of tolerance).A VIF bigger than 10 indicates the multicollinearity.In this study, the lowest of the tolerance and the highest of the VIF were 0.355 and 2.817, respectively, these indices don't confirm multicollinearity in the variables.

Results
In this study, data of 172 MS patients were analyzed.The mean age of participants was 39.39 ± 8.71 years and ranged from 22 to 59 years.The MS duration was 8.29 ± 4.06 years that varied from 2 to 22 years.Table 1 presents frequency distribution of demographic characteristics of the participants.The majority (73.8%) were female and (77.91%) were unemployed.The results showed that most participants were infected to primary progressive and relapsing-remitting types of MS as (38.4%) and (32%) respectively.
As mentioned above multicollinearity determines important changes in the values of the regression coefficients.The tolerance and the variance inflation factor were used to check the assumption of multicollinearity.Table 2 shows the results and confirms the no multicollinearity in variables.
Table 3 presents the descriptive statistics including the minimum, maximum, mean and standard deviation of the variables.
Pearson coefficients was used to assess the correlation between research variables and the results are shown in Table 4.There was a direct significant correlation between negative illness perception and fatigue severity (p < 0.001) while there was an inverse significant correlation between other studied variables.Internal locus of control, self-efficacy, patient activation level, physical activity level, negative coping strategy, and outcome expectancy had the highest negative correlation with fatigue severity, respectively.In addition, all the correlation among variables were significant except the  coefficients of outcome expectancy with negative illness perception, negative coping strategy and physical activity level.
In the next step the model investigated using multiple linear regression (MLR) method.For this way, a separate standard multiple linear regression (Enter) was conducted for each of the endogenous variables.Table 5 shows that the F statistics and analysis of variance is significant, i.e., there is indeed a linear dependence between the dependent variable and the regressor variable (p-value < 0.05) except between the Negative illness perception and the Outcome expectancy.As can be seen, in outcome expectancy variable F is not significant.Table 5 shows the performance of the primary model and coefficients of determination (R 2 ).Table 6 shows the coefficients of the primary model and the results of the t-test, used to study the significance of the regression coefficients (β).P-values < 0.05 were considered statistically significant.By comparing the path coefficients, the relative importance of the influence of endogenous and exogenous variables on the dependent variable was determined in the theoretical model.After removing non-significant variable and paths, the final model was formed and used to determine the paths coefficients and R 2 .
As shown in Table 6 all the paths except the path between Negative coping strategy with Fatigue severity, Outcome expectancy with Fatigue severity, Negative coping strategy with Physical activity level, Internal locus of control with Physical activity level, Outcome expectancy with Physical activity level and Outcome expectancy with patient activation measure are significant.
Tables 7 and 8 shows the statistics of the final model which formed after removing the no significant variable and paths.It is known that 62% of the variance of fatigue severity is explained by the final model.
After removing the no significant variable and paths, the final model was depicted and the path coefficients (β) and explained variance (R 2 ) were determined which are shown in Fig. 2.
As shown in Fig. 2, self-efficacy and internal locus of control have direct and indirect effect on the fatigue severity, but the negative coping strategy only has an indirect effect through patient activation measure on the fatigue severity.
The direct, indirect and total effect of research variables on the fatigue severity in patients with MS can be observed in Table 9.
The Sobel z-value which indicates the significance of the reduction rate of the relation severity between the independent and dependent variable after the entrance of the mediating variable, was obtained 6.78 for the self-efficacy mediating variable; 6.35 for internal locus of control, and 4.05 for negative coping strategy.

Discussion
The aim of the current study was identifying and integrating variables affecting fatigue and applying the results in fatigue management which investigated the mediating role of self-efficacy, internal locus of control, negative coping strategy, and outcome expectancy of fatigue in the relationship between negative illness perception with fatigue severity in MS patients, based on cognitivebehavioral and social cognitive theories.
This study revealed a significant direct relationship between negative illness perception and fatigue severity, as well as a significant indirect relationship through the mediating role of the three variables of internal locus of control, self-efficacy, and negative coping strategy.However, the mediating role of the outcome expectancy variable was not significant.Findings of the research are consistent with the studies that employed similar frameworks to explain the relationships between variables.Recent researches on fatigue self-management behaviors demonstrated that theoretical constructs of social cognitive theory, particularly self-efficacy, may act as a positive  factor affecting on behavior change in reducing fatigue resulted from cancer and MS [16,17].In addition, a significant correlation between locus of control and fatigue was confirmed in a Korean study [24] and positive correlation of external locus of control and negative correlation of internal locus of control with fatigue severity is observed in patients with chronic obstructive pulmonary disease [18].Our results were aligned with the results of mentioned studies.Different studies showed the effect of psychological factors on fatigue and the critical dynamic interaction between illness perception and coping behavior.Therefore, in developing and use the therapeutic interventions for fatigue management, the effect of these psychological   factors such as coping strategies and illness perception should be considered [4,20].Ragg et al. studied patients with chronic fatigue syndrome (CFS).In their study investigate the relationship between health locus of control and functioning.The results indicated that an internal health locus of control was positively related to precipitants' functioning.They also showed that internal health locus of control could successfully predict functioning measured at this study.They therefore concluded that increasing a patient's sense of control would aid CFS recovery [19].In another study, the relationship between illness perceptions, coping, and the perceived severity effect of fatigue evaluated in rheumatoid arthritis (RA) patients.The results showed cognitive representations are different in RA patients with high and low level of fatigue.Compared to less fatigued patients, more fatigued patients reported more emotional symptoms, tendency to differentiate between different types of fatigue, and more perceived outcomes with more severity.More fatigued group often experienced actual control loss in fatigue management and a general preference for suppressing symptoms associated with fatigue.This finding is similar with the significant role of negative coping in this study and shows that the higher emotional load in more tired patients reduces the potential of positive coping strategies and conduct the person to use the negative coping strategies (avoidance or suppression).Moreover, the finding can justify the greater weight of the locus of control in fatigue management [35], that is consistent with the present study results that there is the highest path coefficient in the relationship between the mediating variable of the internal control and the severity of fatigue.Moreover, the relationship between illness perception and coping strategies with fatigue in patients with sarcoidosis revealed a correlation between fatigue and emotional representation.They showed outcome perception explained 37% of fatigue by conducting stepwise regression [21].
In line of our results, the role of illness perception, coping strategy and self-efficacy in compliance with preventive measures of coronavirus infection is demonstrated by Chong et al. study.They showed a direct effect of illness perception and indirect effect through the mediating role of avoidance coping strategy and self-efficacy [22].In addition, a direct effect of illness perception on physical health and fatigue and an indirect effect through avoidance strategies and social support on physical health observed in Marta Bassi study in MS patients [9].
Cheng et al. [44] showed that coping strategy is a promising pathway for managing chronic diseases and believe that appropriate coping strategy may have positive effects on health-related outcomes.In addition, a linear and inverse relationship between self-efficacy and fatigue level in others studies as our results could emphasize the importance of modifying illness perception and strengthen suitable coping strategies [45][46][47].Some other researchers, however, have acknowledged no relationship between fatigue severity and self-efficacy [24,48,49].
The current study results are consistent with most previous studies but unique property of this study is concentrating on the importance and impact of cognition in the relationships among the discussed variables and the possibility of integrating them in order to provide a unified framework as it can mediate the relationship between illness perception and fatigue severity.

Limitations
Despite its strengths and promising results, the current study faced limitations.First, it utilized self-report measures which could affect the accuracy of responses.Second, the sample size was small, which might have impacted the validity and reliability of results.Furthermore, the results may have limited external validity that is because of selecting our sample from Multiple Sclerosis Society members of Qom (a city in Iran).The study's findings as well have restricted generalizability to MS patients with more severe disabilities who are unable to visit the society on an outpatient basis.Accordingly, it is suggested that future studies investigate this issue with a larger sample size, in wider populations and different levels of disability due to multiple sclerosis.
Moreover, based on the positive results of this study in confirming the investigated model, it seems that there is a potential to develop a treatment protocol for fatigue management by using the model which can be the subject of further studies.

Conclusion
In this study, the data of 172 participants who are members of the Qom MS Association (Iran) were analyzed using the multiple linear regression method.The results showing the effect of all variables, except the outcome expectation in the relationship between the negative illness perception with fatigue severity.These variables with their influence, were able to explain 62% of the variance of fatigue severity, which indicates the powerful influence of predictor variables on the dependent variable.Accordingly, and as proven in this study, variables of self-efficacy, internal locus of control, and negative coping strategy can be entered in an integrated structure for the development of fatigue management program has enhanced the expectation of improving the patients' ability in the face of fatigue and consequently enjoying a better quality of life.

Fig. 2
Fig. 2 The final model, variance and path coefficients

Table 1
Demographic characteristics in participants

Table 2
The multicollinearity indexes for regression analysis

Table 3
Descriptive statistics of variables

Table 5
Model summary of the primary model MLR analysis

Table 6
Standardized and Unstandardized coefficients with p-values of the primary model MLR analysis

Table 7
Model summary of the final model MLR analysis

Table 8
Standardized and Unstandardized coefficients with p-values of the final model MLR analysis

Table 9
Direct, Indirect and Total effects of variables on the fatigue severity